: In this revised new application from a young independent investigator, a series of biophysical studies are proposed to investigate the mechanisms underlying the hypothesized coordinate regulation of papillomaviral transcription and papillomaviral DNA replication. The PI, Dr. Alexander, hypothesizes that this coordinate regulation is a consequence of competition between cellular transcription and replication factors and the viral E1 and E2 protein that regulate and contribute to transcription and replication. The aims of this proposal are to evaluate the influence of these factors on each other's DNA binding, protein binding and enzymatic activities. The data gained from this study will be used to create a dynamic model of HPV transcription and replication control that will be broadly applicable to transcription and replication control in DNA viruses.